HUMAN DEFENSES VS DISEASE
I. OVERVIEW A. DEFINITION OF TERMS --RESISTANCE --the ability to ward off disease --SUSCEPTIBILITY --the vulnerability or lack of resistance to disease
B. HOST DEFENSES (HOST DEFENSE MECHANISMS) NON-SPECIFIC RESISTANCE
1ST LINE OF DEFENSE
2ND LINE OF DEFENSE
--intact skin --mucous membranes and their secretions --normal flora
--phagocytic WBC --inflammation and fever --antimicrobial substances
SPECIFIC RESISTANCE 3RD LINE OF DEFENSE
--specialized lymphocytes (B cells and T cells) --antibodies
HOST DEFENSES 1. Non-specific Resistance --natural resistance --defenses that protect us against any pathogen, regardless of species --2 lines of defense: a. First line of defense– skin and mucous membranes b. Second line of defense -- non-specific cellular and chemical responses to microbial invasion -- phagocytes, inflammation, fever, antimicrobial subs. --innate or inherited immune responses
HOST DEFENSES 2. Specific Resistance or Immunity --3rd line of defense --defense directed against a specific microbe --based on specialized cells of the immune system (lymphocytes) and the production of specific proteins (antibodies)
II. FIRST LINE OF DEFENSE A. MECHANICAL BARRIERS 1. Intact skin—provides a complete external covering for the body 2. Mucous membranes—lines the GIT, respiratory tract, GUT -- epithelial layer and an underlying connective tissue layer 3. Tears (lacrimal apparatus) --dilute and wash away irritating substances or microorganisms. 4. Saliva—dilute and wash away microbes from teeth and mouth. 5. Cilia of the respiratory tract -- filter inhaled air and trap microbes, dust, pollutants 6. Epiglottis—prevents microbes from entering lower respiratory tract during swallowing 7. Flow of urine—cleanses urethra and prevents microbial colonization 8. Vaginal secretions
B. CHEMICAL BARRIERS 1. Sebum --contains unsaturated fatty acid --inhibit the growth of certain pathogenic bacteria and fungi 2. Lysozyme --found in resp. tract, tears, saliva, nasal secretions, blood and tissue fluids --capable of breaking down cell walls of gram (+) bacteria and to a lesser extent gram (-) bacteria 3. Gastric juice and digestive enzyme
C. INDIGENOUS MICROFLORA (NORMAL FLORA) --microbial antagonism --factors: 1. Competition for colonization sites 2. Competition for nutrients 3. Production of substances that kill other bacteria (bacteriocins)
III. SECOND LINE OF DEFENSE A.
PHAGOCYTOSIS -- ingestion of an microorganism or any particulate matter by a cell -- phagocytes– types of WBC -- rids of body of unwanted and often harmful substances (dead cells, unused cellular secretions , debris and MO) -- Phagocytic cells: 1. Granulocytes a. Neutrophils or PMNs - highly phagocytic and motile -- active in initial stages of infection b. Eosinophils - phagocytic and can leave blood -- major function: produce toxic proteins against certain parasites
2. Agranulocytes a. Monocytes -- not actively phagocytic b. Macrophages -- mature form of monocytes -- 2 types: b.1 wandering macrophages—migrate to infected areas b.2 fixed macrophages (histiocytes) -- remain in tissues and organs -- trap foreign debris
PHASES OF PHAGOCYTOSIS: 1. Chemotaxis - chemical attraction of phagocytes to MO 2. Attachment or adherence -- attachment of phagocytes plasma membrane to the surface of the MO or other foreign material 3. Ingestion -- forms pseudopods that engulf microbe and form phagosome or phagocytic vesicle 4. Digestion -- Phagosome + lysosome = phagolysosome -- lysosomal enzymes
B. INFLAMMATION
-- Functions: 1. Localize an infection 3. Neutralize toxins 2. Prevent spread of MO 4. Aid in repair and healing -- Classic s/sx: -- rubor, dolor, calor, tumor and functio laesa -- Stages: 1. Vasodilatation and increased permeability of blood vessels 2. Phagocyte migration and phagocytosis 3. Tissue repair
C. FEVER -- Elevation of body temperature that exceeds the normal N = 36.2 - 37.5 C -- fever - >37.8 C -- substances that stimulate the production of fever pyrogens or pyrogenic substances 1. Exogenous pyrogens a. whole MO b. microbial products c. Microbial toxins (enterotoxin, endotoxin) 2. Endogenous pyrogens -- pyrogenic cytokines
FEVER SEPTICEMIA (G RAM (-) BACTERIA) ENDOTOXIN (BLD.STREAM) PHAGOCYTES(ENDOTOXIN) IL-1 HYPOTHALAMUS PROSTAGLANDIN HYPOTHALAMIC THERMOSTAT BODY TEMPERATURE
VASOCONSTRICTION
D. ANTIMICROBIAL SUBSTANCES 1. Cellular secretions a. Interferons (IFN) Antiviral CHONS produced in response to viral infections 3 types: IFN-a, IFN-b, IFN-y Function: interfere with viral multiplication Host-cell specific not virus-specific b. Interleukins (IL) Polypeptides secreted by macrophages and lymphocytes Enhance T lymphocyte activation, proliferation and activity.
2. Blood Proteins A. Complement Group of 30 different CHONS found in plasma Complement system (classical or alternative) Results to: - initiation and amplification of inflammation - chemotaxis - activation of leukocytes - lysis of bacteria - opsonization ( Phagocytosis)
OPSONIZATION - process by which phagocytosis is facilitated by the deposition of opsonins (antibodies or certain complement fragments) B. Prostaglandins (PG) Lipids that act like hormones Play a role in fever, platelet aggregation,immune response, inflammation, pain production, autoimmune response.
THIRD LINE OF DEFENSE: IMMUNE RESPONSE A. The Immune Response (Immune System) B. Immunity C. Antigens and Antibodies
A. THE IMMUNE RESPONSE (IMMUNE SYSTEM) Specific Host Defense Mechanisms 1. Humoral Immunity - always involves the production of antibodies - antibodies play a major role in humoral immunity 2. Cell-Mediated Immunity (CMI) - involves many different cell types - macrophages, T helper cells, cytotoxic T cells, delayed hypersensitivity cells, natural killer cells and granulocytes. - although antibodies may play a role in some types of cell-mediated immune reactions (they do not play a major role)
B. IMMUNITY The
condition of being immune or resistant to a particular infectious disease Acquired Immunity - immunity that results from the active production or receipt of antibodies
ACQUIRED IMMUNITY NATURALLY ACQUIRED
ACTIVE -Antigens enter the body and the body produces antibodies -Clinical or subclinical disease
PASSIVE -Antibodies pass from mother to fetus -Congenital, colostrum
ARTIFICIALLY ACQUIRED ACTIVE -Antigens introduced by vaccines, body produaces antibodies -Vaccines: -Inactivated (killed) - Attenuated (weakened) -Extracts -Toxoids
PASSIVE -Preformed antibodies introduceaaa to body -Antiserum -Antitoxin -Gammaglobulin
TYPES OF VACCINES: 1. Inactivated (killed) -Viruses - hepatitis B, polio (SQ), rabies - Bacteria - anthrax, cholera, pertussis, typhoid fever (SQ) 2. Attenuated (weakened) - Viruses - measles, mumps, rubella, polio (oral) - Bacteria - BCG, typhoid fever (oral) 3. Extracts - bacterial capsular antigen - Hib, meningococcal, pneumococcal 4. Toxoids - Bacteria - diphtheria, tetanus
C. ANTIGENS AND ANTIBODIES 1. Antigens (Ag) - also called immunogens - chemical substance that causes the body to produce specific antibodies - foreign organic substance - antibody generating substance 2. Antibodies (Ab) -also called immunoglobulins (Ig) - glycoproteins produced by lymphocytes in response to the presence of an antigen.
CLASSES A. Ig G - principal circulating Ab - prevalent in serum - provides naturally acquired passive immunity - neutralizes bacterial toxins - participates in complement fixation - enhances phagocytosis B. Ig A - first line of Ab defense against organisms entering through mucous membranes - major Ab in breast milk and other secretions
c. Ig M - largest - first Ab synthesized after Ag stimulation - more efficient than Ig G in complement fixation - involved in agglutination - bactericidal to gram (-) bacteria d. Ig D - fetal antigen receptor - controls antigen stimulation of B-cells e. Ig E - binds very tightly to mast cells and leukocytes (basophils) - causes allergies, drug sensitivity, anaphylaxis and immediate hypersensitivity; combats parasitic diseases